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Sequential ED-design for Binary Dose-response Experiments

Thursday, October 26, 2017 -
16:00 to 17:00
Xiaoli Yu, UBC PhD Student in Statistics
Seminar
Room 4192, Earth Sciences Building (2207 Main Mall)

Dose-response experiments and subsequent data analyses are often carried out according to optimal designs for the purpose of accurately determining a specific effective dose (ED) level. If the interest is the dose-response relationship over a range of ED levels, many existing optimal designs are misaligned. In this dissertation, we propose a new design procedure, called two-stage sequential ED-design, which directly and simultaneously targets several ED levels. We use a small number of trials to provide a tentative estimation of the model parameters. The doses of the subsequent trials are then selected sequentially, based on the latest model information, to maximize the efficiency of the ED estimation over several ED levels.

Although the commonly used logistic and probit models are convenient summaries of the dose-response relationship, they can be too restrictive. We introduce and study a more flexible albeit slightly more complex three-parameter logistic dose-response model. We explore the effectiveness of the sequential ED-design and the D-optimal design under this model, and develop an effective model fitting strategy. We develop a two-step iterative algorithm to compute the maximum likelihood estimate of the model parameters. We prove that the algorithm iteration increases the likelihood value, and therefore will lead to at least a local maximum of the likelihood function. We also study the numerical solution to the D-optimal design for the three-parameter logistic model.  Interestingly, all our numerical solutions to the D-optimal design are three-support distributions.

We also discuss the use of the ED-design when experimental subjects become available in groups.  We introduce the group sequential ED-design, and demonstrate how to construct this design. The ED-design has a natural extension to more complex models, and can satisfy a broad range of the demands that may arise in applications.